Editorial: Immunosenescence after sepsis

COPYRIGHT © 2023 Lu and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Editorial PUBLISHED 10 March 2023 DOI 10.3389/fimmu.2023.1177148


Immune cell senescence related to organ dysfunction in sepsis
Immune cell senescence is manifested by a decrease in number and function of immune cells (3). Lu et al. summarized the possible mechanisms of immunosenescence and parenchymal organ damage. Sepsis-induced oxidative stress may lead to a decrease in cellular telomerase activity and telomere shortening. Age-related methylation in the nuclei and mitochondrial DNA is a kind of reprogramming of immune cells, which is a significant manifestation of immunosuppression. Otherwise, the inhibition of immune checkpoints, such as programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), is considered as a method to improve immunosuppression (4). However, the relevance of immune checkpoint regulation to immunosenescence is still worth testing.
The effects of immunosenescence on solid organs after sepsis have been observed in the lungs, brain, heart, kidneys, and liver. Senescent immune cells in the lungs could lead to decreased cell proliferation and impaired cytokine secretion. There's a high susceptibility to lung disease. Immunosenescence could disrupt the intrinsic barrier of the brain and release pro-inflammatory mediators. On the other hand, immunosenescence after sepsis may lead to local myocardial ischemia or infarction secondary to coronary artery disease and renal dysfunction. Although liver damage appears in the early stages of sepsis, the effect of immunosenescence on liver injury deserves further investigation.
Inhibition of myeloid-derived suppressor cell amplification in sepsis may improve patient outcomes

Sepsis prognosis can be predicted by immune genes
The search for immune markers is helpful for the treatment and prognosis prediction of sepsis. The research of Liu et al. pointed a novel immune gene that could be valuable for predicting the outcome of sepsis patients. Through analysis of public databases and validation of the sepsis patient cohort, FCGR2C was considered to have good predictive efficacy. FCGR2C was also found to be closely related to a variety of immune cell functions. Cytotoxic lymphocytes were significantly increased in the sepsis death group, and FCGR2C was negatively correlated with cytotoxic lymphocytes. As a biomarker of bacterial infection, the role of red blood cell distribution width (RDW) in sepsis was systematically reviewed by Wu et al. Finally, RDW is considered to be a feasible and sensitive biomarker for predicting mortality in patients with sepsis.

The prognostic model of sepsis can guide the clinical use of medications
The differentially expressed genes (DEGs) associated with sepsis can be found by single-cell RNA sequencing (scRNA-seq) and transcriptome RNA-seq. He et al. built a prognostic model of sepsis with DEGs including CCL5, HBD, IFR2BP2, LTB, and WFDC1. The risk prediction model and enrichment analysis showed that there was a difference in the abundance of immune cells in low -and high-risk sepsis patients. Treg cells, CD4 memory activated T cells, resting NK cells, M0 and M2 macrophages were higher in the high-risk group than in the lowrisk group. They further analyzed immunotherapeutic targets of commonly used immune-related drugs in sepsis, such as immunostimulatory drugs, immunostimulatory cytokines, and immunosuppressants. Nine target sites were identified, of which IL-7 is considered to be the most promising immunotherapy.

Summary
The immune status of sepsis is very complex and results from the combination of excessive inflammatory response and immunosuppression. Our Research Topic was ranging from mechanisms of immunosuppression, immune gene-related prognostic indicators, to monitoring clinical drug targets in sepsis. Immunosenescence is a novel study of sepsis immunity. We can learn from its mechanism of action in tumor microenvironment to further explore its influence on sepsis. As representative cells of sepsis immunosuppression, MDSCs had been reported for the first time to show proliferative inhibition in pediatric sepsis by CRRT treatment. The discovery of immune-related genes may be complementary to predict the prognosis of sepsis. Our Research Topic provides a new idea to study the mechanism of sepsis immunosuppression and paves the way for the clinical transformation of sepsis immunotherapy.
We thank all authors of this Research Topic, as well as the reviewers for their contributions.

Author contributions
XL contributed to the drafting of this Editorial. Y-QL made critical revisions and finalized the Editorial. All authors contributed to the article and approved the submitted version.

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